1. Field of the Invention
This invention relates to a novel class of compounds which may be used as novel crosslinking agents to prepare novel UV-curable hydrophilic copolymers suitable for use as articles in the biomedical field, especially contact lenses.
2. Background
In the field of crosslinked polymeric systems, initiators, and crosslinking compounds and compositions (crosslinkers) are often added to monomer mixes before polymerization. These crosslinkers facilitate formation of the desired polymer. In addition, crosslinkers can affect specific characteristics and mechanical properties of the resultant polymers.
Crosslinkers which are similar in structure to the monomers being reacted are often added to monomer mixtures. For example, a di(meth)acrylate or di(meth)acrylamide monomer would commonly be used as a crosslinker for a (meth)acrylate/(meth)acrylamide system. Alternatively, to react a vinyl-type system comprising N-vinyl pyrrolidone or vinyl acetate, for example, a vinyl-type crosslinker such as allyl methacrylate would ordinarily be used. For the purposes of this application, the terms, "vinyl-type" or "vinyl-containing" refer to those non-acrylic monomers having the vinyl grouping (CH.sub.2 .dbd.CH--), and which are generally reactive. "Acrylic-type" or "acrylic-containing" monomers refer to those monomers containing the acrylic grouping (CH.sub.2 .dbd.CRCOX--).
When a specific copolymeric system is desired which includes both a methacrylate-containing monomer and a non-acrylic vinyl-containing monomer, polymerization problems occur as a result of the varying reactivity of the two monomer types. In other words, non-acrylic vinyl-containing monomers are generally not reactive with the (meth)acrylate-containing monomers.
Therefore, to copolymerize N-vinyl pyrrolidone (NVP) with, for example, methyl methacrylate (MMA), allyl methacrylate has been used as a crosslinker with t-butylperoxyoctoate added as a thermal reaction initiator, and benzoin methyl ether (BME) as a photoinitiator. Such a monomer mix may then be first subjected to UV irradiation to polymerize the methacrylate groups, followed by heat curing to polymerize the allyl- and vinyl-containing monomers. This polymerization scheme is relatively cumbersome and may lead to polymeric systems having poor yields or a resulting polymer of poor optical quality. In addition, such resulting polymers may not be true crosslinked copolymers but may be mere nonhomogeneous interpenetrating polymer networks.
Alternately, a crosslinker such as allyl methacrylate could be used to assist the polymerization of the NVP/methacrylate system; however, this would also require heat curing. Heat curing is not as desirable as UV curing since over-heating may adversely affect the desired properties of the end-product hydrogel. In addition, insufficient heat curing can result in a hydrogel which also fails to possess the desired end-result properties.
Other known crosslinking agents often used in polymeric syntheses are polyvinyl, typically di- or tri-vinyl monomers, most commonly the di- or tri(meth)acrylates of dihydric ethylene glycol, triethylene glycol, butylene glycol, hexane-1,6-diol, thio-diethylene glycol-diacrylate and methacrylate; neopentyl glycol diacrylate; trimethylolpropane triacrylate and the like; N,N'-dihydroxyethylenebisacrylamide and -bismethacrylamides; also diallyl compounds like diallyl phthalate and triallyl cyanurate; divinylbenzene; ethylene glycol divinyl ether; and the (meth)acrylate esters of polyols such as triethanolamine, glycerol, pentanerythritol, butylene glycol, mannitol, and sorbitol. Further, illustrations include N,N-methylene-bis-(meth)acrylamide, sulfonated divinylbenzene, and divinylsulfone. Also useful are the reaction products of hydroxyalkyl (meth)acrylates with unsaturated isocyanates, for example the reaction product of 2-hydroxyethyl methacrylate with 2-isocyanatoethyl methacrylate (IEM) as disclosed in U.S. Pat. No. 4,954,587.
Other known crosslinking agents are the polyether-bisurethane-dimethacrylates as described in U.S. Pat. No. 4,192,827, and those crosslinkers obtained by reaction of polyethylene glycol, polypropylene glycol and polytetramethylene glycol with 2-isocyanatoethyl methacrylate (IEM) or m-isopropenyl-.gamma.,.gamma.-dimethylbenzyl isocyanates (m-TMI), and polysiloxane-bisurethane-dimethacrylates as described in U.S. Pat. Nos. 4,486,577 and 4,605,712. Still other known crosslinking agents are the reaction products of polyvinyl alcohol, ethoxylated polyvinyl alcohol or of polyvinyl alcohol-co-ethylene with 0.1 to 10 mol % vinyl isocyanates like IEM or m-TMI. However, none of the above-mentioned crosslinkers can be used to copolymerize vinyl and acrylic comonomers using only UV curing.
It is also known that NVP copolymerizes well with vinyl carbonates and vinyl carbamates. Specifically, NVP was shown to copolymerize with vinylene carbonate. The closeness of the reactivity ratios resulted in favorable random copolymerization. (See K. Hayashi and G. Smets, J. Polymer Science, Vol. 27, p. 275, (1958)). Further, it has been recently demonstrated that NVP can copolymerize with vinyl carbamates and carbonates with a UV sensitive initiator. (See U.S. Pat. No. 5,070,215).
It was discovered in the field that certain crosslinked polymeric materials could be hydrated and retain their water content. It was further found that the higher the water content within contact lenses made from these crosslinked hydrogel polymers, the greater was the oxygen permeability through the lens to the cornea.
In the field of contact lenses, various factors combine to yield a material that has appropriate characteristics. Oxygen permeability, wettability, material strength and stability are but a few of the factors which must be carefully balanced to achieve a useable end-result contact lens. Generally, as the water content of a hydrogel increases, oxygen permeability also increases. Since the cornea receives its oxygen supply exclusively from contact with the atmosphere, good oxygen permeability is a critical characteristic for any contact lens material.
In the case of hydrogel preparation, the crosslinkers affect specific mechanical properties relating to the firmness of the hydrogel, such as modulus, and tear strength. As a result, it is desirable in the field of hydrogel synthesis to introduce specific crosslinkers to copolymerize in a predictable way with the comonomers in the monomer mix, thereby creating hydrogels having certain desired properties.
A hydrogel is a hydrated crosslinked polymeric system that contains water in an equilibrium state. The physical properties of hydrogels can vary widely and are mostly determined by their water content. Hydrogels may contain 10% to 90% water by weight and exhibit excellent biocompatibilty. As a result there has been extensive interest in the use of hydrogels for various biomedical applications as biomedical devices. For example, hydrogels can be used as contact lenses, intraocular implants, membranes and other films, diaphragms, catheters, mouth guards, denture liners, tissue replacements, heart valves, intrauterine devices, ureter prostheses, etc. Commercial success for hydrogels has been found in the field of ophthamology, most particularly as contact lenses.
The use of hydrogels to make contact lenses has been known, since at least as early as Wichterle, et al., U.S. Pat. No. 3,220,960 which discloses hydrogels involving a hydrated polymer of an hydroxyalkyl acrylate or methacrylate crosslinked with a corresponding diester. Particularly, poly(2-hydroxyethyl methacrylate), also known as poly-HEMA, was disclosed as an illustrative hydrogel having a water content of about 39% by weight. Hydrogels such as 2-hydroxyethyl methacrylate with water contents of about 40% by weight, are often referred to as low water content hydrogels.
Another known hydrogel system is comprised of copolymers of N-vinyl pyrrolidone (NVP) and a methacrylate, such as methyl methacrylate (MMA). The water content of the NVP-MMA hydrogel systems can vary widely as a function of the ratio of NVP to MMA. However, most hydrogels derived from NVP and MMA which are of commercial interest have a water content in the 70% to 80% by weight range. Hydrogels containing N,N-dimethylacrylamide copolymers (DMA) are known to have similar properties. Hydrogels containing water weight percents in this range are often referred to as high water content hydrogels.
High water-containing hydrogels have at times exhibited undesirable mechanical properties. For example, such hydrogels are not easily formed into hydrolytically stable lenses. Further such materials have at times exhibited tearing or other breakage as a result of poor tensile strength. What was needed was a highly oxygen permeable material that was durable and highly wettable. Wettability is important in that if the lens is not sufficiently wettable, it does not remain lubricated and therefore cannot be worn comfortably on the eye. The optimal contact lens would have not only excellent oxygen permeability, but also excellent tear fluid wettability.
As a general rule, low water content hydrogels have acceptable properties for application as soft contact lenses. High water content hydrogels appear to have acceptable oxygen permeability suitable for use as extended wear lenses. Extended wear lenses are those worn without removal for periods of time longer than a day. However, high water content hydrogels are often not easily formed into stable lenses. Such high water-containing lenses have been reported to tear more easily, and may otherwise be more prone to damage.
Theoretically, the most desirable lens would have oxygen transmissibility at least as high as that of lenses comprising the NVP-MMA system, while also having strength and mechanical properties similar to lenses made from the poly-HEMA hydrogels.
Silicone-containing materials were tried as viable contact lens materials and displayed very good oxygen permeability and durability. However, most silicone-containing materials are largely hydrophobic and therefore not sufficiently wettable. Further, it is believed that such hydrophobicity causes deposit problems, which may result in discomfort when wearing contact lenses made from these silicone-containing polymers. The optimum contact lens would have not only excellent oxygen permeability, but also excellent tear-fluid wettability.
As mentioned previously, curing hydrogels solely with UV radiation would be preferable to heat curing. However, no completely UV curable acrylic/vinyl- or styrene/vinyl-or acrylic/vinyl/styrene-crosslinked polymeric system, is presently known. Such a UV-curable polymeric hydrogel system employing a crosslinker able to compatibilize groups of varying reactivities would be highly advantageous.